Various species of Cimicifuga have been used as therapeutics for inflammatory conditions in Chinese, Korean, and Japanese medicine. Similarly, compositions containing black cohosh, known botanically as Cimicifuga racemosa L. Nutt (also Actaea racemosa), are widely used as herbal dietary supplements in the United States and Europe. Historically, Native American women used black cohosh for the treatment of malaise, malaria, rheumatism, abnormal kidney function, sore throat, menstrual irregularities, and diseases associated with childbirth (Blementhal et al., 2000). In Asian countries, this herb and other species of Cimicifuga including Cimicifuga dahurica (Turcz.) Maxim., Cimicifuga foetida L., and Cimicifuga heracleifolia Kom. are used to treat inflammation, fever, headache, pain, sore throat, and chills (Foster, 1999; Kusano, 2001; Kim et al., 2004). However, the underlying mechanisms of action for these herbs remain to be fully elucidated.
The biological activities of black cohosh have been investigated previously. In vivo, it was demonstrated that black cohosh extracts inhibit the anti-IgE-induced passive cutaneous anaphylaxis reaction in Sprague-Dawley rats in a dose-dependent manner (Kim et al., 2004). In vitro, the herbal extracts inhibit the transcription of cytokines including IL-4, IL-5 and TNF-α by inflammatory agents such as PMA and A2387 in HMC-1 human leukemia mast cells (Kim et al., 2004). Other studies also demonstrated the inhibitory effects of black cohosh extract on histamine, bradykinin and COX-2 mediated inflammatory actions (Kim and Kim, 2000). However, the active components present in the extract are unknown.
Cimiracemate A is the ester formed between isoferulic acid and 3-(30,40-dihyroxylphenyl)-2-keto-propanol (Chen et al., 2005). Cimiracemate A is a naturally occurring compound possessing a 1,7-diaryl skeleton. Other compounds with this 1,7-diaryl skeleton have significant biological activities (Roughley & Whiting, 1973). For instance, curcumin, a natural pigment isolated from Curcuma longa has been reported to inhibit growth of several types of malignant cells (Chen et al., 1999; Aggarwal et al., 2004) and especially in the case of HIV infection (Vlietinck et al., 1998). Yakuchinone B extracted from the seeds of Alpina oxyphylla (Itokawa et al., 1982) is active against hypercholesterolemia and atherosclerosis (Ohishi et al., 2001).
Cimiracemate A has been found to suppress LPS-induced TNF-α in human macrophages and to inhibit LPS-induced MAP kinase activities as well as activation of specific transcription factors. Furthermore, cimiracemate A may have additional health benefits including reactive oxygen species scavengers (Burdette et al., 2002). Taken together, compounds, like cimiracemate A, with the 1,7-diaryl skeleton may have multiple bioactivities that can act via multiple cell-dependent mechanisms.
C. racemosa has been experiencing a dramatic increase in consumption in the United States and Europe. Its products are prepared in the form of isopropanolic and ethanolic extracts currently available to consumers in a range of formulations and dosages. The use of this herb has been based on extracts rather than the individual bioactive components. Although some compounds have been isolated from C. racemosa, including triterpene glycosides and phenolics, their bioactivities and consistent presence in the extracts remain to be determined (Kennelly et al., 2002).
Another isolated C. racemosa component is 23-epi-26-deoxyactein. The 23-epi-26-deoxyactein component is currently used as the chemical marker to standardize commercial C. racemosa products. The rationale for its usage is its abundance in the extract (Pepping, 1999). Thus, the chemical marker used for the standardization of C. racemosa extracts is not necessarily representative of the bioactivity of this herb.
Many different species of cimicifuga are traditionally used to cure inflammation; however, as indicated in FIG. 10, their chemical constituents are relatively different under the same analyzing condition. Although different methods have been developed to distinguish Cimicifuga species using fingerprinting approach (He et al., 2006; Li et al., 2002), the complexity and the variation of the chemical constituents of the herbs limit their use in species identification.
Therefore, a great need exists for the extraction and isolation of cimiracemate A for subsequent use as a therapeutic agent. In addition, there is a need for a bioactive marker that can be used to identify the members of the Cimicifuga genus, for example: C. racemosa, C. dahurica (Turcz.) Maxim., C. foetida L., and C. heracleifolia Kom. Ideally the bioactive marker could can also be used to standardize extracts of Cimicifuga species for use as anti-inflammatory agents for the treatment of inflammatory-associated diseases and to distinguish species based on the chemical profile of each sample.